The present invention relates to an antibody or antibody fragment modified by chemical linkage to a synthetic poly(amide/urea/thiourea) which contains a plurality of boron atoms or other functional groups, conferring upon the resultant conjugate desirable properties as a diagnostic and/or therapeutic agent.
It is known to modify antibodies by chemically linking to them various types of addends. For example, enzymes have been linked to antibodies to make conjugates useful in ELISA immunoassays, boron-containing addends have been linked to antibodies and antibody fragments to produce therapeutic agents, and antibodies have been conjugated to polypeptides such as polylysine. European patent application No. 88,695, to McKearn et al., published 9/14/83, discloses antibodies conjugated to polypeptides made from natural amino acids, which in turn can carry a functional group such as a chelator, drug, toxin and the like.
It would be highly desirable to be able to modify an immunoglobulin to incorporate moieties that contain useful functionality, but in such a way that the addend is precisely defined in terms of its structure. This is particularly useful where it is desired to incorporate a plurality, especially a large number, of added functional groups such as chelating agents, boron-containing groups, radionuclides, spin labels and the like. In the past, it has been troublesome to attempt to characterize such modified antibodies because of the heterogeneity of the conjugates, and this has resulted in difficulties in assuring reproducibility of results. Moreover, it has been difficult to attach sufficient boron atoms to an antibody so that even a low percentage of conjugates localized in tumor or lesion tissue carries a large enough number of boron atoms to be therapeutically significant for neutron activated radiotherapy.
A need therefore continues to exist for chemically modified antibody conjugates having well-defined structures for the modifying groups to minimize the uncertainties in preparing and using these molecular species.